Dobrazanski P, Noguchi T, Kovary K, Rizzo C A, Lazo P S, Bravo R
Department of Molecular Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000.
Mol Cell Biol. 1991 Nov;11(11):5470-8. doi: 10.1128/mcb.11.11.5470-5478.1991.
We demonstrate that a member of the fos family, the fosB gene, gives rise to two transcripts by alternative splicing of exon 4, generating two proteins, FosB of 338 amino acids and a short form, FosB/SF, which contains the DNA binding and dimerization domains but not the 101 amino acids of the C terminus. FosB/SF activates an AP-1-chloramphenicol acetyltransferase construct in NIH 3T3 cells, as determined by transient and stable transfections, although more weakly than does FosB. In contrast to FosB, FosB/SF has lost its ability to repress the dyad symmetry element of the c-fos gene. FosB/SF when expressed in excess to FosB can downmodulate the activity of FosB. Constitutive expression of high levels of FosB/SF in NIH 3T3 cells has no significant inhibitory effect in the induction of cell proliferation or cell cycle progression, indicating that FosB/SF is not a negative regulator of cell growth. This conclusion is further confirmed by the observation that the majority of the Jun molecules are complexed with FosB/SF in the FosB/SF-overexpressing cells.
我们证明,fos家族的一个成员fosB基因通过外显子4的可变剪接产生两种转录本,生成两种蛋白质,即338个氨基酸的FosB和一种短形式FosB/SF,后者包含DNA结合和二聚化结构域,但不包含C末端的101个氨基酸。通过瞬时转染和稳定转染测定,FosB/SF可激活NIH 3T3细胞中的AP-1-氯霉素乙酰转移酶构建体,尽管其活性比FosB弱。与FosB不同,FosB/SF已失去抑制c-fos基因二元对称元件的能力。当FosB/SF的表达量超过FosB时,它可以下调FosB的活性。在NIH 3T3细胞中组成型表达高水平的FosB/SF对细胞增殖或细胞周期进程的诱导没有显著抑制作用,这表明FosB/SF不是细胞生长的负调节因子。在FosB/SF过表达细胞中,大多数Jun分子与FosB/SF复合,这一观察结果进一步证实了这一结论。